Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MRL-Mp-lpr/lpr mice contain phenotypically abnormal populations of T cells, and exhibit an SLE-like autoimmune disease in which autoantibodies are a prominent feature. We analyzed the phenotype and T-cell receptor V beta expression pattern in CD4+ T cells of this mutant mouse strain to detect abnormalities that could explain the autoimmunity. The CD4+ T cells contain two distinct abnormal populations. One of these expresses B220 and HSA, and in these and other respects closely resembles the accumulating CD4-CD8- population. The other expresses a high level of CD44 (Pgp-1), and a high level of the 16A epitope of CD45, and so resembles post-activation T cells. Both of these cell types are exclusive to MRL-Mp-lpr/lpr. We also identified V beta 5- and V beta 11-positive CD4+ T cells, in both MRL-Mp-lpr/lpr and MRL-Mp-+/+ mice. We conclude that autoimmune T cells can be detected in these mice, but that they are not the cause of the accumulation of abnormal CD4+ and CD4-CD8- cells.
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PMID:Self-reactivity and the expression of memory markers vary independently in MRL-Mp+/+ and MRL-Mp-lpr/lpr mice. 134 99

Murine CD3+,CD4-,CD8- peripheral T cells, which express various forms of the TCR-gamma delta on their cell surface, have been characterized in terms of their cell-surface phenotype, proliferative and lytic potential, and lymphokine-producing capabilities. Three-color flow cytofluorometric analysis demonstrated that freshly isolated CD3+,CD4-, CD8- TCR-gamma delta lymph node cells were predominantly Thy-1+,CD5dull,IL-2R-,HSA-,B220-, and approximately 70% Ly-6C+ and 70% Pgp-1+. After CD3+,CD4-,CD8-splenocytes were expanded for 7 days in vitro with anti-CD3-epsilon mAb (145-2C11) and IL-2, the majority of the TCR-gamma delta cells expressed B220 and IL-2R, and 10 to 20% were CD8+. In comparison to CD8+ TCR-alpha beta T cells, the population of CD8+ TCR-gamma delta-bearing T cells exhibited reduced levels of CD8, and about 70% of the CD8+ TCR-gamma delta cells did not express Lyt-3 on the cell surface. Functional studies demonstrated that splenic TCR-gamma delta cells proliferated when stimulated with mAb directed against CD3-epsilon, Thy-1, and Ly-6C, but not when incubated with an anti-TCR V beta 8 mAb, consistent with the lack of TCR-alpha beta expression. In addition, activated CD3+,CD4-,CD8- peripheral murine TCR-gamma delta cells were capable of lysing syngeneic FcR-bearing targets in the presence of anti-CD3-epsilon mAb and the NK-sensitive cell line, YAC-1, in the absence of anti-CD3-epsilon mAb. Finally, activated CD3+, CD4-,CD8-,TCR-gamma delta+ splenocytes were also capable of producing IL-2, IL-3, IFN-gamma, and TNF when stimulated in vitro with anti-CD3-epsilon mAb.
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PMID:Phenotypic and functional analysis of murine CD3+,CD4-,CD8- TCR-gamma delta-expressing peripheral T cells. 252 34

Lymph node cells from C3H mice homozygous for lpr and gld were compared for expression of cell surface antigens, lectin-binding sites, functional characteristics, expression of ecotropic MuLV, and organization of Ig and T cell receptor (TcR) beta-chain genes. The abnormal cells (Ly-2-/L3T4-) populating nodes of both mutant strains were specifically purified by using plate separation techniques. The purified abnormal cells were shown to express the beta-chain of the TcR, to exhibit rearrangements of the beta-chain genes, and to express TcR beta and alpha gene mRNA, demonstrating the T cell origin of these populations. FMF analyses of the separated abnormal cells showed them to be Thy-1+, Ly-1+, Ly-2-, L3T4-, Ly-5(B220)+, Ly-6+, Ly-22+, Ly-24+, sIg-, ThB-, Ia-, HSA-/+, and PC.1+ and to bind at high levels lectins that normally bind preferentially to B cells. These cells did not proliferate or generate CTL in response to stimulation with alloantigens, and supernatants of cells stimulated with Con A were devoid of IL 2. These characteristics do not correspond to those of any known immature or mature population of normal T cells. The findings that the abnormal T cells of lpr and gld homozygotes are indistinguishable for each parameter examined support the suggestion that these mutations may affect different enzymes in a common metabolic pathway of major importance to T cell differentiation and function.
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PMID:Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gld mice. 300 14

Immunization of mice for contact sensitivity induces two different antigen-specific Thy-1+ cell activities that are required to act in sequence for elicitation of contact sensitivity. In this study, 2,4-dinitro-1-fluorobenzene contact sensitivity responses in BALB/c and C3H/He mice demonstrated the importance of early-acting and antigen-specific contact sensitivity-initiating cells to recruit the classical, late-acting contact sensitivity effector T cells. Employing in vitro treatment of sensitized cells with monoclonal antibodies to cell surface determinants and then incubation in complement, prior to adoptive cell transfer, the contact sensitivity-initiating cells were shown to have a surface phenotype that is quite unusual for antigen-specific cells [Thy-1+, CD5+, CD3-, CD4-, CD8-, sIg-, B220+, major histocompatibility complex class II-, CD23+, IL-2R-, IL-3R+, Mel-14-, CD44+ (Pgp-1+), J11d+ (HSA+), MAC-1+, LFA-1+, and Fc gamma IIR+], and is quite different from the late-acting, contact sensitivity-effector T cells (Thy-1+, CD5+, CD3+, CD4+, CD8-, sIg-, B220-, major histocompatibility complex class II-, CD23-, IL-2R+, IL-3R-, and CD44- (Pgp-1-), J11d-(HSA-), MAC-1-, LFA-1+, Fc gamma IIR-). Contact sensitivity initiation was required for elicitation of late 24-h 2,4-dinitro-1-fluorobenzene contact sensitivity responses, in both BALB/c and C3H/He mice. Moreover, relatively high doses of some monoclonal antibodies [anti-B220 (CD45RA) and anti-CD23 (IgE Fc epsilon II receptor)] were necessary to completely eliminate all contact sensitivity-initiating cells that permitted expression of late contact sensitivity-effector T-cell activity. In contrast, high doses of monoclonal antibody specific for surface determinants of late-acting contact sensitivity effector T cells (anti-CD3 and anti-CD4), when used in high doses similar to anti-B220 and anti-CD23, had no effect on contact sensitivity-initiating cell activity. Our results indicate that two very different antigen-specific Thy-1+ cells are necessary to elicit 2,4-dinitro-1-fluorobenzene contact sensitivity in BALB/c and C3H/He mice.
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PMID:DNFB contact sensitivity (CS) in BALB/c and C3H/He mice: requirement for early-occurring, early-acting, antigen-specific, CS-initiating cells with an unusual phenotype (Thy-1+, CD5+, CD3-, CD4-, CD8-, sIg-, B220+, MHC class II-, CD23+, IL-2R-, IL-3R+, Mel-14-, Pgp-1+, J11d+, MAC-1+, LFA-1+, and Fc gamma RII+). 750 36

Four thymic epithelial cell lines (TEC) were derived from neonatal CBA and non-obese diabetic (NOD) mouse thymus. From these cell lines a series of clones were produced by limit dilution and these have remained in stable culture for more than 1 year. Morphological characterization indicates that most cells are stellate with numerous short or long processes and ultrastructural studies show both active and quiescent cells with junctional complexes and bundles of tonofibrils. Immunohistochemical and flow cytometric analyses show that the cells express cytokeratin and appear to label for markers characteristic of cortical epithelial cells. Most clones express Thy-1, Pgp-1, ICAM-1, HSA and B220 antigen, but are negative for LFA-1, CD2, Mel 14, Fc receptor, Mac-1, CD4 and CD8. All clones express low to moderate levels of class I MHC but are either negative or extremely low for class II MHC antigen. Most clones secrete IL-6 and granulocyte-macrophage-CSF (GM-CSF) in vitro, but generally do not produce IL-2, IL-3, IL-4 or IFN-gamma.
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PMID:Production and characterization of mouse thymic epithelial cell clones. 751 33

Regulation of B lymphocyte development by the mu-membrane (mu m) and delta-membrane (delta m) heavy chains of Ig was examined in an Ig transgenic mouse model. Mice were bred on a common C57BL/6 (B6) background, and expressed rearranged and hypermutated heavy and light chain transgenes encoding high-affinity receptors for the foreign antigen hen egg lysozyme (HEL). At no stage were they exposed to HEL. Variation of the Ig heavy chain construct yielded four different types of Ig transgenic mice in which developing B lineage cells either expressed mu m and delta m in the normal physiological sequence (mu m then mu m + delta m), or produced mu m alone, delta m alone or mu m + delta m from the onset of heavy chain expression in the bone marrow. Immature B220low, HSAhigh and mature B220high, HSAlow B cells were produced in all mice regardless of their developmental pattern of mu m and delta m expression. However, production of immature B cells was most efficient when mu m heavy chain was expressed alone during early B cell development. Thus expression of delta m during this period either in the presence or absence of mu m resulted in a 2- to 3-fold reduction in the numbers of immature B cells in the spleen as well as altered levels of surface B220 and HSA on these cells in spleen and bone marrow respectively. By contrast, normal maturationally regulated expression of delta m led to the presence of increased numbers of mature B cells in the spleen and lengthened the average lifespan of these cells as determined by in vivo incorporation of 5-bromo-2'-deoxyuridine. These results pointed to selective effects of mu m and delta m heavy chains on regulation of the early and late stages of B cell development respectively, and provided a rational basis for co-expression of mu m and delta m as well as the delayed expression of delta m during normal B cell development.
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PMID:Differential regulation of early and late stages of B lymphocyte development by the mu and delta membrane heavy chains of Ig. 769 8

The elicitation in immunized mice of delayed-type hypersensitivity (DTH) responses to nickel sulfate (NiSO4) was found to be mediated by the sequential activities of two different antigen-specific Thy-1+ cells. Early-acting (2-hr) NiSO4-specific, DTH-initiating cells were required for elicitation of subsequent 24-hr NiSO4-specific DTH and had an unusual phenotype for an antigen-specific cell (Thy-1+, CD5+, CD3-, CD4-, CD8- CD23+, CD45RA+ (B220+), IL-2R-, IL-3R+, sIg-, MHC Class II-, Mel-14-, CD44+ (Pgp-1+), J11d+ (HSA+), MAC-1+, LFA-1, and Fc gamma II-R+). In contrast, the late-acting, NiSO4-specific DTH-effector T cells were: Thy-1+, CD5+, CD3+, CD4+, CD8-, CD23-, B220-, IL-2R+, IL-3R-, sIg-, MHC Class II-, Mel-14+, CD44- (Pgp-1-), J11d- (HSA-), MAC-1-, LFA-1+, and Fc gamma II-R-. Our results led us to surmise that the early-acting DTH-initiating cells were necessary to locally recruit the late-acting effector T cells. Relatively high doses of anti-B220 (CD45RA) and anti-CD23 (IgE Fc epsilon RII receptor) monoclonal antibodies were necessary to completely eliminate all DTH-initiating cells, and therefore completely block subsequent expression of some late NiSO4-specific DTH activity that was due to the late-acting DTH effector T cells. In addition, we found that mast cells were important for expression of early-acting, DTH-initiating cell activity in this NiSO4-specific, DTH system. This was probably due to the absence of mast cells in mast cell-deficient WBB6F1-W/Wv mice. Our results indicated that two different antigen-specific Thy-1+ cells are necessary to elicit NiSO4-specific DTH in mice and that mast cells are necessary for expression of the early component that is due to early-acting, DTH-initiating cells.
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PMID:Elicitation of nickel sulfate (NiSO4)-specific delayed-type hypersensitivity requires early-occurring and early-acting, NiSO4-specific DTH-initiating cells with an unusual mixed phenotype for an antigen-specific cell. 769 35

Prior studies in the human have implied an important function for CD10 (CALLA, neutral endopeptidase 24.11) in early lymphoid development. To examine the role of this ectoenzyme in an experimental system, a rat mAb specific for mouse CD10, termed R103, was generated. Immunohistological and flow cytometric analyses indicate that the distribution of CD10 in non-lymphoid anatomical compartments is virtually identical in human and mouse. However, CD10 expression within the hematopoietic system is strikingly different. In contrast to human spleen, lymph node and thymus, the corresponding mouse organs contain no detectable CD10+ cells. Mouse granulocytes, unlike human granulocytes, also lack CD10 expression. Five-color flow cytometric studies of adult bone marrow (BM) from C57BL/6 and BALB/c mice with mAb specific for CD43, B220, HSA, BP-1 and immunoglobulin M fail to detect any significant number of CD10+ cells at pro-B, pre-B or B cell stages. In addition, lymphoid cells in both (rIL-7) independent and rIL-7-dependent in vitro pro-B cell cultures lack CD10 expression. Consistent with this result, CD10 mRNA is not detected. Unlike the AA4.1+ population from day 13 and 14 fetal liver, the CD10+ subset is unable to reconstitute T and B lymphoid compartments in RAG-2-/- mice. Nevertheless, mouse CD10 is readily found on BM stromal elements known to support early B lineage lymphoid development. Given the common expression of CD10 on human and mouse BM stromal elements, this enzyme may have an important function in the stromal cell-dependent phase of hematopoiesis.
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PMID:The distribution of CD10 (NEP 24.11, CALLA) in humans and mice is similar in non-lymphoid organs but differs within the hematopoietic system: absence on murine T and B lymphoid progenitors. 770 96

v-mpl is a constitutively activated, truncated form of a cytokine receptor that has been transduced in a murine retrovirus, the myeloproliferative leukemia virus (MPLV). Expression of this oncogene results in the factor-independent proliferation of myeloid, erythroid, megakaryocytic, and mast precursor cells, which retain the ability to differentiate. However, no lymphoid disease was ever reported. To determine whether MPLV could infect and transform very early B cells and their precursors (BCPs), lymphoid long-term bone marrow cultures were infected with a helper-free MPLV. Within 3 wk after infection, highly proliferating BCPs could be isolated. These cells were able to clone spontaneously in semi-solid cultures, grown in the absence of feeder cell layer or exogenous growth factor and rapidly produced tumors after s.c. injection into synegic irradiated mice. In addition, MPLV transformation of pre-B cells led to the induction of an autocrine activity. Immunophenotypic and molecular analysis indicated that MPLV transformed early pro-B, pro-B, and pre-B cells, according to the expression of HSA, CD43, B220, Thy1, s-IgM and BP1 Ags, and to the rearrangements of Ig genes. Interestingly, MPLV-transformed BCPs expressed Mac1 Ag without acquiring further characteristics of macrophagic differentiation. Although the v-mpl cytoplasmic domain is devoid of tyrosine kinase consensus sequence, MPLV-transformed pre-B cells contained a major approximately 105-kDa tyrosine-phosphorylated protein that was not detected in uninfected cells or in cells transformed by the Abelson viral oncogene (v-abl). These results demonstrate that, like v-abl, the truncated cytokine receptor v-mpl is able to transform BCPs in vitro and suggest that the oncogenic transformation of BCPs by either v-mpl or v-abl use different pathways.
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PMID:In vitro transformation of murine pro-B and pre-B cells by v-mpl, a truncated form of a cytokine receptor. 783 43

Multiple cytokines can synergize to stimulate the in vitro proliferation and exclusive myeloid differentiation of multipotent bone marrow progenitor cells. The ligand for c-kit (stem cell factor [SCF]) plays a key role in stimulating myeloid and erythroid cell production of primitive hematopoietic progenitors. SCF in combination with interleukin-7 (IL-7) can also stimulate the combined myeloid and B-cell differentiation of uncommitted hematopoietic progenitor cells as well as the growth of early B-cell progenitor cells, although the involvement of c-kit in early B lymphopoiesis remains controversial. In the present study, the flt3-ligand (FL), which, in combination with other cytokines, has overlapping activities with SCF on myeloid cell production from uncommitted progenitors, was investigated for its ability to induce selective stroma-independent B-cell commitment from uncommitted Lin-Sca-1+ bone marrow progenitor cells. IL-7 alone did not induce any clonal growth and FL alone gave rise to a few clusters (< 50 cells) but no colonies (> 50 cells), whereas the combined stimulation with FL and IL-7 resulted in clonal growth of 10% of Lin-Sca-1+ bone marrow cells. After 12 days of incubation of Lin-Sca-1+ cells in FL + IL-7, an almost 400-fold increase in cell production was observed. Phenotyping showed that greater than 99% of the cells produced were of the B-cell lineage, in that they expressed B220, but not cell surface markers specific for myeloid, erythroid, or T-cell lineages. Furthermore, the cells did not express cytoplasmic mu-heavy chain (cmu) or surface IgM, but were positive for CD24 (heat stable antigen [HSA]) and CD43 (leukosialin), suggesting that the cells produced were blocked at a late pro-B-cell stage. Interestingly, although all FL + IL-7-responsive Lin-Sca-1+ progenitor cells and the resulting pro-B cells expressed c-kit, FL + IL-7 was much more potent (62-fold) than SCF + IL-7 in stimulating production of cells of the B-cell lineage. In addition, whereas FL + IL-7 selectively stimulated the production of pro-B cells, SCF + IL-7 predominantly stimulated the production of mature granulocytes. Replating studies showed that FL + IL-7-responsive Lin-Sca-1+ progenitors were not committed to the B-cell lineage, because after 2 days of incubation in FL + IL-7, 80% of the progenitors retained a myeloid potential. As much as 27% of the FL + IL-7-responsive progenitors remained uncommitted after 7 days of incubation, but all had committed to the B-cell lineage after 10 days of incubation in FL + IL-7. These results show that FL much more potently and selectively than SCF synergizes with IL-7 to enhance B-cell commitment and development from uncommitted progenitor cells.
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PMID:Combined signaling through interleukin-7 receptors and flt3 but not c-kit potently and selectively promotes B-cell commitment and differentiation from uncommitted murine bone marrow progenitor cells. 869 43


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